tbuckley/cabot-search huggingface dataset:
Innate immune receptor signaling induces transient melanoma dedifferentiation while preserving immunogenicity
Authors: Beatrice Thier, Fang Zhao, Simone Stupia, Alicia Brüggemann, Johannes Koch, Nina Schulze, Susanne Horn, Christoph Coch, Gunther Hartmann, Antje Sucker, Dirk Schadendorf, Annette Paschen
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune-stimulatory agents, like agonists of the innate immune receptor RIG-I, are currently tested in clinical trials as an intratumoral treatment option for patients with unresectable melanoma, aiming to enhance anti-tumor T cell responses. Switching of melanoma toward a dedifferentiated cell state has recently been linked to T cell and therapy resistance. It remains to be determined whether RIG-I agonists affect melanoma differentiation, potentially leading to T cell resistance. Methods Patient metastases-derived melanoma cell lines were treated with the synthetic RIG-I agonist 3pRNA, and effects on tumor cell survival, phenotype and differentiation were determined. Transcriptomic data sets from cell lines and metastases were analyzed for associations between RIG-I (DDX58) and melanoma differentiation markers and used to define signaling pathways involved in RIG-I-driven dedifferentiation. The impact of 3pRNA-induced melanoma dedifferentiation on CD8 T cell activation was studied in autologous tumor T cell models. Results RIG-I activation by 3pRNA induced apoptosis in a subpopulation of melanoma cells, while the majority of tumor cells switched into a non-proliferative cell state. Those persisters displayed a dedifferentiated cell phenotype, marked by downregulation of the melanocytic lineage transcription factor MITF and its target genes, including melanoma differentiation antigens (MDA). Transition into the MITF low /MDA low cell state was JAK-dependent, with some cells acquiring nerve growth factor receptor expression. MITF low /MDA low persisters switched back to the proliferative differentiated cell state when RIG-I signaling declined. Consistent with our in vitro findings, an association between melanoma dedifferentiation and high RIG-I (DDX58) levels was detected in transcriptomic data from patient metastases. Notably, despite their dedifferentiated cell phenotype, 3pRNA-induced MITF low /MDA low persisters were still efficiently targeted by autologous CD8 tumor-infiltrating T lymphocytes (TILs). Conclusions Our results demonstrate that RIG-I signaling in melanoma cells drives a transient phenotypic switch toward a non-proliferative dedifferentiated persister cell state. Despite their dedifferentiation, those persisters are highly immunogenic and sensitive toward autologous TILs, challenging the concept of melanoma dedifferentiation as a general indicator of T cell resistance. In sum, our findings support the application of RIG-I agonists as a therapeutic tool for the generation of long-term clinical benefit in non-resectable melanoma.
Treatment with tumour necrosis factor inhibitors is associated with a time-shifted retardation of radiographic spinal progression in patients with axial spondyloarthritis
Authors: Murat Torgutalp, Valeria Rios Rodriguez, Ani Dilbaryan, Fabian Proft, Mikhail Protopopov, Maryna Verba, Judith Rademacher, Hildrun Haibel, Joachim Sieper, Martin Rudwaleit, Denis Poddubnyy
Journal: Annals of the Rheumatic Diseases (2022)

The objective of the current study was to analyse the association between treatment with tumour necrosis factor inhibitors (TNFi) and radiographic spinal progression in patients with axial spondyloarthritis (axSpA) from a long-term inception cohort.
Non-electric bioelectrical analog strategy by a biophysical-driven nano-micro spatial anisotropic scaffold for regulating stem cell niche and tissue regeneration in a neuronal therapy
Authors: Xiangyun Yao, Lei Zhan, Zhiwen Yan, Juehong Li, Lingchi Kong, Xu Wang, Huimin Xiao, Huiquan Jiang, Chen Huang, Yuanming Ouyang, Yun Qian, Cunyi Fan
Journal: Bioactive Materials (2022)

The slow regenerating rate and misdirected axonal growth are primary concerns that disturb the curative outcome of peripheral nerve repair. Biophysical intervention through nerve scaffolds can provide efficient, tunable and sustainable guidance for nerve regrowth. Herein, we fabricate the reduced graphene oxide (rGO)/polycaprolactone (PCL) scaffold characterized with anisotropic microfibers and oriented nanogrooves by electrospinning technique. Adipose-derived stem cells (ADSCs) are seeded on the scaffolds in vitro and the viability, neural differentiation efficiency and neurotrophic potential are investigated. RGO/PCL conduits reprogram the phenotype of seeded cells and efficiently repair 15 mm sciatic nerve defect in rats. In summary, biophysical cues on nerve scaffolds are key determinants to stem cell phenotype, and ADSC-seeded rGO/PCL oriented scaffolds are promising, controllable and sustainable approaches to enable peripheral nerve regeneration.
6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice
Authors: Kassem Makki, Harald Brolin, Natalia Petersen, Marcus Henricsson, Dan Ploug Christensen, Muhammad Tanweer Khan, Annika Wahlström, Per-Olof Bergh, Valentina Tremaroli, Kristina Schoonjans, Hanns-Ulrich Marschall, Fredrik Bäckhed
Journal: Gut (2022)

Objective Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising the fibres. Here, we investigated whether the soluble dietary fibre oligofructose improves host metabolism by modulating bacterial transformation of secondary bile acids in mice fed western-style diet. Design To assess the impact of dietary fibre supplementation on bile acid transformation by gut bacteria, we fed conventional wild-type and TGR5 knockout mice western-style diet enriched or not with cellulose or oligofructose. In addition, we used germ-free mice and in vitro cultures to evaluate the activity of bacteria to transform bile acids in the caecal content of mice fed with western-style diet enriched with oligofructose. Finally, we treated wild-type and TGR5 knockout mice orally with hyodeoxycholic acid to assess its antidiabetic effects. Results We show that oligofructose sustains the production of 6α-hydroxylated bile acids from primary bile acids by gut bacteria when fed western-style diet. Mechanistically, we demonstrated that the effects of oligofructose on 6α-hydroxylated bile acids were microbiota dependent and specifically required functional TGR5 signalling to reduce body weight gain and improve glucose metabolism. Furthermore, we show that the 6α-hydroxylated bile acid hyodeoxycholic acid stimulates TGR5 signalling, in vitro and in vivo, and increases GLP-1R activity to improve host glucose metabolism. Conclusion Modulation of the gut microbiota with oligofructose enriches bacteria involved in 6α-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice.
Association of Interpregnancy Interval With Adverse Birth Outcomes
Authors: Ting Xu, Huazhang Miao, Yuliang Chen, Limei Luo, Pi Guo, Yingxian Zhu
Journal: JAMA Network Open (2022)

Many studies have reported an association of interpregnancy interval (IPI) between 2 consecutive births with adverse birth outcomes in low- and middle-income countries. However, most of these studies ignore the implications of some unmeasured confounders.To explore the association of IPI with adverse perinatal outcomes.This large-scale cohort study used the Guangdong Provincial Women and Children Health Information System in Guangdong Province, China, to obtain birth data recorded between January 1, 2014, and December 31, 2020. Matched-sibling design was used. The final cohort included first-born and second-born sibling pairs delivered by mothers who were permanent residents of Guangdong Province.The exposure variable was IPI, which was categorized as follows: less than 6, 6 to 11, 12 to 17, 18 to 23, 24 to 29, 30 to 35, and 36 or more months.The outcome variables were adverse birth outcomes: preterm birth (PTB, gestational age <37 weeks), low birth weight (LBW, <2500 g), and small for gestational age (SGA). Adjusted odds ratio (OR) and interaction odds ratio (IOR) associated with IPI were calculated.The study consisted of 725 392 sibling pairs of multiparous mothers. Among these mothers, 718 111 (99.0%) were aged 20 to 34 years, and 715 583 (98.7%) were of Han Chinese ethnicity. Unmatched analysis showed that a short IPI of less than 6 months was associated with higher risks of PTB (adjusted OR, 1.96; 95% CI, 1.87-2.06), LBW (adjusted OR, 1.88; 95% CI, 1.79-1.98), and SGA (adjusted OR, 1.34; 95% CI, 1.30-1.38) compared with an IPI of 18 to 23 months. These associations were attenuated in the matched-sibling analysis. An association of short IPI (<6 months) with PTB (adjusted IOR, 1.40; 95% CI, 1.30-1.51), LBW (adjusted IOR, 1.30; 95% CI, 1.21-1.40), and SGA (adjusted IOR, 1.16; 95% CI, 1.11-1.22) remained in the matched analysis. For IPI of 36 months or more, the odds of PTB (adjusted OR, 1.08; 95% CI, 1.03-1.14) and LBW (adjusted OR, 1.13; 95% CI, 1.07-1.19) in the unmatched analysis were also greater than the reference interval (18-23 months), but not for SGA (adjusted OR, 0.96; 95% CI, 0.93-0.99). Associations between a long IPI (≥36 months) and PTB (adjusted IOR, 1.10; 95% CI, 1.02-1.19) and LBW (adjusted IOR, 1.16; 95% CI, 1.07-1.26) remained through the sibling comparisons.Results of this study indicated that mothers with a short (<6 months) or long (≥36 months) IPI had greater odds of adverse birth outcomes. The findings may inform family planning policies and guide individuals and families who are planning for another pregnancy in China.
Prospective Evaluation of Cardiovascular Risk 10 Years After a Hypertensive Disorder of Pregnancy
Authors: Lisa D. Levine, Bonnie Ky, Julio A. Chirinos, Jessica Koshinksi, Zoltan Arany, Valerie Riis, Michal A. Elovitz, Nathanael Koelper, Jennifer Lewey
Journal: Journal of the American College of Cardiology (2022)
Differentiation of Reversible Hemichorea Due to Vitamin B12 Deficiency From Huntington Disease Via FDG PET
Authors: Tabea Schroeter, Falk Gühne, Matthias Schwab, Robert Drescher, Hubertus Axer
Journal: Clinical Nuclear Medicine (2022)

Abstract Vitamin B12 deficiency may present with diverse symptoms, complicating the differential diagnosis. Extrapyramidal movement disorders, for instance, are a rare manifestation of vitamin B12 deficiency. MRI of the brain frequently remains without conclusive findings. However, 18 F-FDG PET/CT may reveal characteristic changes in the metabolism of the basal ganglia and thus contribute to an accurate diagnosis. We demonstrate the case of a woman with left-sided hemichoreatic movements due to vitamin B12 deficiency showing a contralateral putaminal hypermetabolism, which normalized after vitamin B12 supplementation, ruling out other deviating causes, particularly Huntington disease.
More Recent Literature Does Not Support Premise or Conclusions
Authors: Timothy R. Shope, Nader Shaikh, Alejandro Hoberman
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension
Authors: Shalina Taylor, Sarasa Isobe, Aiqin Cao, Kévin Contrepois, Bérénice A. Benayoun, Lihua Jiang, Lingli Wang, Stavros Melemenidis, Mehmet O. Ozen, Shoichiro Otsuki, Tsutomu Shinohara, Andrew J. Sweatt, Jordan Kaplan, Jan-Renier Moonen, David P. Marciano, Mingxia Gu, Kazuya Miyagawa, Brandon Hayes, Raymond G. Sierra, Christopher J. Kupitz, Patricia A. Del Rosario, Andrew Hsi, A. A. Roger Thompson, Maria E. Ariza, Utkan Demirci, Roham T. Zamanian, Francois Haddad, Mark R. Nicolls, Michael P. Snyder, Marlene Rabinovitch
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear. Objectives: To relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling. Methods: Production of elastase, release of extracellular traps, adhesion, and migration were assessed in neutrophils from patients with pulmonary arterial hypertension and control subjects. Proteomic analyses were applied to explain functional perturbations, and transcriptomic data were used to find underlying mechanisms. CD66b-specific neutrophil EVs were isolated from plasma of patients with pulmonary arterial hypertension, and we determined whether they produce pulmonary hypertension in mice. Measurements and Main Results: Neutrophils from patients with pulmonary arterial hypertension produce and release increased neutrophil elastase, associated with enhanced extracellular traps. They exhibit reduced migration and increased adhesion attributed to elevated β1-integrin and vinculin identified by proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic IFN signature that we related to an increase in human endogenous retrovirus K envelope protein. Transfection of human endogenous retrovirus K envelope in a neutrophil cell line (HL-60) increases neutrophil elastase and IFN genes, whereas vinculin is increased by human endogenous retrovirus K deoxyuridine triphosphate diphosphatase that is elevated in patient plasma. Neutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus K envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor. Conclusions: Elevated human endogenous retroviral elements and elastase link a neutrophil innate immune response to pulmonary arterial hypertension.
Correction:<i>British Thoracic Society Winter Meeting November 2021</i>
Journal: Thorax (2022)

service evaluation of laboratory and clinical management of NTM-LD in a large teaching hospital in England Amendments to text in abstracts P189 -Use of Angiotensin-Converting-Enzyme Inhibitors and Angiotensin Receptor Blockers in COVID-19 infection does not adversely affect clinical outcomes including need for Non-Invasive and Invasive Ventilation Amendment to table P7 -Remote Frailty Assessment and Prevalence of Frailty in Older Outpatients with Idiopathic Pulmonary Fibrosis Correction 1 of 2
Errors in Labeling Figures 1 and 2
Journal: JAMA Network Open (2022)

Hong-Qiu Gu, PhD; Xin Yang, MD; Chun-Juan Wang, MD; Xing-Quan Zhao, MD; Yi-Long Wang, MD; Li-Ping Liu, MD; Xia Meng, MD; Yong Jiang, PhD; Hao Li, MD, PhD; Chelsea Liu, MHS; Yun-Yun Xiong, MD; Gregg C. Fonarow, MD; David Wang, MD; Ying Xian, MD, PhD; Zi-Xiao Li, MD; Yong-Jun Wang, MD, PhD
Mortality Among Patients Undergoing Blood Transfusion in Relation to Donor Sex and Parity
Authors: Jingcheng Zhao, Arvid Sjölander, Gustaf Edgren
Journal: JAMA Internal Medicine (2022)

Prior evidence suggests that plasma and platelet transfusions from female and parous donors are associated with adverse clinical outcomes, which has led to the predominant use of male donors for plasma and platelets in many countries. However, studies on red blood cell transfusions have been conflicting.
Errors in Title and Byline
Journal: JAMA Network Open (2022)

Amanda Brown Marusiak, MPH; Brandon D. Hollingsworth, PhD; Haley Abernathy, BS; Aidin Alejo, BS; Victor Arahirwa, BS; Odai Mansour, BS ; Dana Giandomenico, MPH; John Schmitz, PhD; Carl Williams, DVM; Alexis M. Barbarin, PhD; Ross M. Boyce, MD, MSc
Implications of the National Institutes of Health Stroke Scale <i>Cookie Theft</i> Picture—A Closer Look
Authors: Sharon N. Poisson, Kelly L. Block, Karen D. Orjuela
Journal: JAMA Neurology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Study of the level of tumor markers and mutations in the BRCA1/2 genes in breast cancer patients with metachronous tumors.
Authors: Sergey Viktorovich Kamishov, Kamila Shavkatovna Izrailbekova, Oleg Yurievich Balenkov
Journal: Journal of Clinical Oncology (2022)

e12563 Background: Primary multiple malignant tumors are more common in women with breast cancer (BC). However, the difference in the frequency of mutations in the BRCA1/2 genes in metachronous BC tumors has not been fully studied, and there are also conflicting data on the increase in the level of specific tumor markers in this category of patients. Methods: The survey included 58 patients with BC with II-III clinical stages of the disease, of which metachronous tumors in terms of 6 months or more were found in 26 (44.8%) patients, among them metachronous cancer of the second breast - in 14 (53 .8%), cancer of the body of the uterus - in 7 (26.9%) and ovarian cancer - in 5 (19.2%) patients. In the control group of 32 (55.2%) patients with initially diagnosed BC, with the same stages of the disease. Tumor markers were determined in the peripheral venous blood of patients using reagent kits for ELISA analysis produced in Russia. The study of mutations in the BRCA1/2 genes was performed using sequencing on the Illumina MiSeq platform in tumor samples from waxed histological blocks. Library sequencing was performed using MiSeq Reagent Kit v2. Results: ELISA analysis of the level of tumor markers in patients with BC showed that with the development of metachronous cancer, the studied markers were more common than in the control group. In patients with metachronous tumors, elevated levels of CA-125 occurred in 10 (38.5%) patients, CA-15-3 - in 8 (30.8%), CA-19-9 - in 4 (15.4%), AFP - in 5 (19.2%), CEA - in 6 (23.1%). In the control group, CA-125 was found in 6 (18.8%) patients, CA-15-3 - in 5 (15.6%), CA-19-9 - in 2 (6.3%), AFP - in 1 (3.1%), CEA - in 2 (6.3%). Excess levels significant for diagnosis were observed for CA-125 and CA-15-3 in both groups of patients, but in the group of patients with BC with metachronous tumors, these figures were approximately 2 times higher. In the rest of the patients, the oncomarkers under consideration did not reach values significant for diagnosis. The total incidence of patients with clinically significant germline variants in the BRCA1/2 genes in the control group was 5 (15.6%), of which there were predominantly patients with an increased frequency in the population (5382insC, 4154del4, C61G). The total incidence of BC patients with metachronous tumors with germline and somatic variants in the BRCA1/2 genes was 16 (61.5%), with an increased frequency in the same population, mainly in patients with germline mutations. Conclusions: Dynamic study of the level of tumor markers CA-125 and CA-15-3 and CA-19-9 may be useful in the preventive examination of patients with a history of BC as an early diagnosis of the development of metachronous tumors in this category of patients. The most important diagnostic unfavorable factor in the development of metachronous tumors in the examined BC patients was germline mutations in the BRCA1/2 genes.
Comparative clinical manifestations and immune effects of cytomegalovirus infections following distinct types of immunosuppression
Authors: David S.Y. Ong, Ga-Lai M. Chong, Roy F. Chemaly, Olaf L. Cremer
Journal: Clinical Microbiology and Infection (2022)

Cytomegalovirus (CMV) infection is a well-recognised complication of solid organ and hematopoietic cell transplantation. However, CMV infection also occurs in patients with human immunodeficiency virus infection, previously immunocompetent intensive care unit patients, and individuals on immunosuppressive medications for various underlying diseases.This review describes the comparative effects of CMV infection in distinct types of acquired immunosuppression.Selected peer-reviewed publications on CMV infections published until December 2021.CMV infection affects various organ systems through direct cytolytic mechanisms but may also exert indirect effects by promoting pro-inflammatory and immunosuppressive responses. This has been well studied in transplant recipients, for whom antiviral prophylaxis and pre-emptive therapy have now become standard practice. These strategies not only prevent direct CMV disease manifestations but also mitigate various immunopathological processes to reduce graft-vs.-host disease, graft rejection, and the occurrence of secondary bacterial and fungal infections. The efficacy of neither prophylactic nor pre-emptive treatment of CMV infection has been demonstrated for patients with critical illness- or medication-induced immunosuppression. Many observational studies have shown an independent association between CMV reactivation and a prolonged duration of mechanical ventilation or increased mortality in the intensive care unit. Furthermore, data suggest that CMV reactivation may increase pulmonary inflammation and prolong the duration of mechanical ventilation.A large number of observational and experimental studies suggest attributable morbidity and mortality related to CMV infection, not only in transplant recipients and patients with human immunodeficiency virus infection but also in patients with critically illness- or medication-induced immunosuppression. Adequately powered randomised controlled trials investigating the efficacy of prophylaxis or pre-emptive treatment of CMV infection in these patients are lacking, with a notable exception for transplant recipients.